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Blood:钠氢交换调控因子(NHERF-2)能够维持内皮细胞的稳定

来源:生物谷 2012-05-20 19:05

近日,美国美国梅奥临床医学院的研究人员发现,钠氢交换调控因子(NHERF-2)能够维持内皮细胞的稳定。相关研究成果于5月17日发表在Blood上。

钠氢交换调控因子(NHERF-2)是几乎所有内皮细胞(ECs)所含有的组分,但是到目前为止,它的功能还不明确。

这里,研究人员表示,NHERF-2是内皮细胞的一个关键性的调节因子。他们发现,在没有有丝分裂原(如VEGF)的环境下,对比于控制组ECs,NHERF-2沉默的ECs仍然能够以很快的速率进行增殖。

进一步研究表明,NHERF-2沉默EC之所以能够表现出高速增殖表型,是因为它具有加速的细胞周期,这可能是被这些因素协同引起的:细胞质钙浓度增加,的c-Myc表增加达,细胞周期蛋白D1表达增加,p27表达下降。

利用人类血管瘤的小鼠模型,他们发现,由NHERF-2沉默细胞引起的内皮细胞瘤,在个体上要大于由控制组细胞所诱导的肿瘤。

Debabrata Mukhopadhyay表示,NHERF-2是内皮增生的一个负调控因子,它对内皮的稳定及血管构建也可能具有重要作用。(生物谷Deepblue编译)

NHERF-2 maintains endothelial homeostasis

Resham Bhattacharya, Enfeng Wang, Shamit K. Dutta, Pawan K. Vohra, Guangqi E, Y. S. Prakash, and Debabrata Mukhopadhyay.

The Na+/H+ exchanger regulatory factor-2 (NHERF-2) is an integral component of almost all endothelial cells (ECs), yet its endothelial function is not known.Here, we found that NHERF-2, is a key regulator of endothelial homeostasis because NHERF-2–silenced ECs proliferate at a much higher rate even in the absence of mitogens such as VEGF compared with control ECs.We further show that the hyperproliferation phenotype of NHERF-2–silenced EC is because of an accelerated cell cycle that is probably caused by a combination of the following factors: increased cytoplasmic calcium, increased expression of c-Myc, increased expression of cyclin D1, and reduced expression of p27.Using an experimental mouse model of human hemangioma, we found that the endothelial neoplasms derived from NHERF-2–silenced cells were much larger in volume than those derived from control cells.Thus, NHERF-2 is a negative regulator of endothelial proliferation and may have important roles in endothelial homeostasis and vascular modeling.

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